Regulation of blood sugar levels is an essential physiological process in vertebrates and invertebrates. In mammals, insulin and glucagon are the two endocrine hormones that maintain a steady-state of glucose levels in the blood by antagonistic functions. Disruption of this process results in serious health problems such as diabetes mellitus. In Drosophila melanoganster, the corpora cardiaca (CC) cells are a cluster of endocrine cells that produce a glucagon-like peptide called Adipokinetic hormone (AKH). Previous studies have shown that CC cells use glucose-sensing and response mechanisms similar to human pancreatic islet cells and are critical regulators of glucose homeostasis in the fly. In addition, many aspects of CC cell development seem to be reminiscent of pancreatic islet development. Thus, we postulate that common mechanisms may regulate development and function of CC cells and other endocrine cells. The aim of this proposal is to identify genes involved in the development and function of CC cells by using a P-element based enhancer trap screen and a candidate gene approach. Loss and gain of function studies will be used to characterize the role of candidate CC cells regulators. In addition, we will identify orthologous mouse genes and will assess the levels of conservation of gene expression between Drosophila CC cells, mammalian endocrine precursor cells and mature islet cells. The long-term goal of this project is to accelerate the discovery of conserved genetic and cellular mechanism regulating endocrine development and function. Relevance of research to public health: Our studies on Drosophila CC cells may guide investigations underlying development, growth, function, and regeneration of organs like endocrine pancreas. This should accelerate discovery of new strategies for diagnosis and treatment of endocrine disorders like diabetes mellitus.